August 29, 2013
The Orphan Drug Act of U.S allows the FDA to give orphan drugs special marketing protections such as seven years of market exclusivity, tax credits to offset some of the costs of development, faster regulatory reviews and additional assistance from FDA reviewers during the development and review process. Thirty years after ratifying the Orphan Drug Act, FDA has made a number of minor revisions to bring its definitions up to date and to eliminate ambiguity by clarifying the content. “FDA believes these revisions will clarify, streamline, and improve the orphan-drug designation process”.
The consultation process began in October 2011, with FDA issuing its final rule on the changes. Some of the key changes include refining the definition of an orphan subset to include “use of the drug in a subset of persons with a non-rare disease or condition may be appropriate but use of the drug outside of that subset (in the remaining persons with the non-rare disease or condition) would be inappropriate owing to some property(ies) of the drug, for example, drug toxicity, mechanism of action, or previous clinical experience with the drug”.
Another important clarification was on whether an orphan drug would still keep its designation and hence the special marketing protection if that drug had more than one indication that finally treated more than 200,000 patients. The final rule concluded that as long as each patient population for which the drug is indicated for is less than 200,000, the drug would still have the protections under the Orphan Drug Act. This, however, does not extend to distinct stages of the same disease (for eg., cancer), unless an acceptable justification was provided.
The FDA also attempted to address “evergreening” of drugs, where some companies try to obtain extended periods of patent exclusivity that is in excess of the approved 7 years by changing a component of the drug, some of which simply includes a dose change. However, no resolution was obtained on this as according to the FDA some dose changes may be “eligible for their own seven-year period of orphan exclusive approval” due to its advanced nature.
The final rule also removed language which implied that clinical superiority would require direct comparison with the approved drug such as providing of non-inferiority trial data. FDA also urged sponsors to include only “relevant” in vitro laboratory data, and “clinical experience” in their application, except in cases of “well-documented case histories or significant human experience with the drug” .